Active agents or drugs that are effective in vitro may not be as effective in vivo due to the delivery difficulties in vivo, in particular, their limited penetration ability across one or more biological barriers before reaching the site of action where diseases occur in vivo.
Currently many drugs are administered through systematic route, such as oral or parenteral administration, to reach the action site of a condition or disease. Since higher dosage of drugs is required to reach a distal location in the systematic administration, drugs delivered by such a route may cause adverse reactions. For example, non-steroidal anti-inflammatory agents (NSAIAs) are widely used for treatment of acute or chronic conditions where pain and inflammation are present. Although NSAIAs are absorbed in the stomach and intestinal mucosa, oral administration usually accompany adverse drug reactions such as gastrointestinal (GI) effects and renal effects. For instance, aspirin is known to cause gastric mucosal cell damage. The side effects of NSAIAs appear to be dose-dependent, and in many cases severe enough to pose the risk of dyspepsia, gastroduodenal bleeding, gastric ulcerations, gastritis, ulcer perforation, and even death.
Modifications of the known NSAIAs have been reported to improve their efficacy and decrease their side effects. However, to treat inflammation or pain at distal areas, a much higher plasma concentration of the active agent is required when the drug is administered orally than when the drug is administered accurately at the particular site of pain or injury (Fishman; Robert, U.S. Pat. No. 7,052,715).
Fishman and many others (Van Engelen et al. U.S. Pat. No. 6,416,772; Macrides et al. U.S. Pat. No. 6,346,278; Kirby et al. U.S. Pat. No. 6,444,234, Pearson et al. U.S. Pat. No. 6,528,040, and Botknecht et al. U.S. Pat. No. 5,885,597) have attempted to develop a delivery system for transdermal application by drug formulation to reduce the side effect associating with oral administration and achieve localized drug administrations with reduced systematic exposure. It is very difficult, however, to deliver therapeutically effective plasma levels of these drugs by the formulation.
Therefore, there is a need to develop novel compositions that are capable of being delivered efficiently and effectively to the action site of a condition (e.g., a disease) to prevent, reduce or treat conditions and minimize side effects.